Yersinia pestis, the causative agent of plague, is among the deadliest infectious agents affecting humans. Transmitted by infected fleas, Y. pestis causes primarily bubonic plague. The disease occasionally evolves to pneumonic plague, the most deadly and contagious form of the infection, which is then transmitted from human to human by aerosols.
Since the beginning of the nineties, plague has been included in the list of re-emerging diseases and Y. pestis is classified as a potential biological weapon for terrorist use. Because antibiotic resistant strains of Y. pestis have been observed or could be engineered for evil use, vaccination against plague might become the only means to fight against the disease.
Most efforts made in the recent years focused on subunit formulations combining the capsular F1 antigen and the V antigen (LcrV). Such vaccines however require the use of an adjuvant and repeated injections to confer a mostly antibody-dependent protection.
Other strategies included the attenuation of live Y. pestis by genetic engineering, the introduction of Y. pestis antigens in Salmonella or virus vectors, and DNA vaccination. However, such vaccines are not sufficiently safe and/or efficient against both bubonic plague and pulmonary plague.
Derbise et al. 2012 [bibliographic reference (1)], which has been published on Feb. 14, 2012, describes the construction of a live vaccine against plague. More precisely, it describes the cloning of the Yersinia pestis caf operon, which codes for surface-expression of the oligomeric Y. pestis F1 antigen and insertion of said operon on a plasmid for electroporation into an attenuated strain of Yersinia pseudotuberculosis. In the resulting Y. pseudotuberculosis strain (strain V674pF1), the nucleic acid coding for surface-expression of the monomer unit of the Y. pestis F1 (i.e., at least the Caf1 polypeptide) is contained in said plasmid.
In the Yersinia pseudotuberculosis cells or strains of the application, the nucleic acid coding for surface-expression of the Caf1 polypeptide is contained in the chromosome of said Y. pseudotuberculosis cells or strains. The application demonstrates an exceptionally high vaccination efficacy against both bubonic plague and pneumonic plague. The application further provides comparative experimental data, which notably demonstrate that the cells or strains of the application are more efficient than the V674pF1 strain described in Derbise et al. 2012.